Retention of Poloxamer-based Hydrogels for Vaginal Application in Mouse and Rat Models

The purpose of this study is to evaluate the retention capabilities of poloxamer-based hydrogels for vaginal application with nonoxinol-9 as the model drug. Two hydrogel formulations, which contained 18% poloxamer 407 plus 1% poloxamer 188 (GEL1, relative hydrophobic) or 6% poloxamer 188 (GEL2, relative hydrophilic), were compared with respect to the rheological properties, hydrogel erosion and drug release. The vaginal retention capabilities of these hydrogel formulations were further determined in two small animal models, including drug quantitation of vaginal rinsing fluid in mice and isotope tracing with Tc in rats. The two formulations exhibited similar phase transition temperatures ranging from 27 to 32 °C. Increasing the content of poloxamer 188 resulted in higher rheological moduli under body temperature, but slightly accelerated hydrogel erosion and drug release. When compared , GEL1 was eliminated significantly slower in rat vagina than GEL2, while the vaginal retention of these two hydrogel formulations behaved similarly in mice. In conclusion, increases in the hydrophilic content of formulations led to faster hydrogel erosion, drug release and intravaginal elimination. Rats appear to be a better animal model than mice to evaluate the hydrogel for vaginal application.